Combined deletions of IHH and NHEJ1 cause chondrodystrophy and embryonic lethality in the Creeper chicken

Commun Biol. 2020 Mar 25;3(1):144. doi: 10.1038/s42003-020-0870-z.


The Creeper (Cp) chicken is characterized by chondrodystrophy in Cp/+ heterozygotes and embryonic lethality in Cp/Cp homozygotes. However, the genes underlying the phenotypes have not been fully known. Here, we show that a 25 kb deletion on chromosome 7, which contains the Indian hedgehog (IHH) and non-homologous end-joining factor 1 (NHEJ1) genes, is responsible for the Cp trait in Japanese bantam chickens. IHH is essential for chondrocyte maturation and is downregulated in the Cp/+ embryos and completely lost in the Cp/Cp embryos. This indicates that chondrodystrophy is caused by the loss of IHH and that chondrocyte maturation is delayed in Cp/+ heterozygotes. The Cp/Cp homozygotes exhibit impaired DNA double-strand break (DSB) repair due to the loss of NHEJ1, resulting in DSB accumulation in the vascular and nervous systems, which leads to apoptosis and early embryonic death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Bone Diseases, Developmental / embryology
  • Bone Diseases, Developmental / genetics
  • Bone Diseases, Developmental / metabolism
  • Bone Diseases, Developmental / veterinary*
  • Bone and Bones / embryology*
  • Bone and Bones / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Chick Embryo
  • DNA Repair Enzymes / deficiency
  • DNA Repair Enzymes / genetics*
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics*
  • Embryonic Development
  • Gene Deletion*
  • Gene Expression Regulation, Developmental
  • Genetic Predisposition to Disease
  • Hedgehog Proteins / deficiency
  • Hedgehog Proteins / genetics*
  • Heterozygote
  • Homozygote
  • Phenotype
  • Poultry Diseases / embryology
  • Poultry Diseases / genetics*
  • Poultry Diseases / metabolism


  • DNA-Binding Proteins
  • Hedgehog Proteins
  • DNA Repair Enzymes